Department of Medicine and Resuscitation Institute, Rosalind Franklin University of Medicine and Science, Ill.
Transl Res. 2013 Aug;162(2):110-21. doi: 10.1016/j.trsl.2013.06.002. Epub 2013 Jun 24.
We investigated the metabolic and functional myocardial effects of erythropoietin (EPO) administered during resuscitation from cardiac arrest using an open-chest pig model of ventricular fibrillation and resuscitation by extracorporeal circulation, after having reported in rats a reversal of postresuscitation myocardial dysfunction associated with activation of mitochondrial protective pathways. Ventricular fibrillation was induced in 16 male domestic pigs and left untreated for 8 minutes, after which extracorporeal circulation was started and maintained for 10 additional minutes, adjusting the extracorporeal flow to provide a coronary perfusion pressure of 10 mmHg. Defibrillation was accomplished and the extracorporeal flow was adjusted to secure a mean aortic pressure of 40 mmHg or greater during spontaneous circulation for up to 120 minutes. Pigs were randomized 1:1 to receive EPO (1200 U/kg) or 0.9% NaCl before starting extracorporeal circulation. Severe postresuscitation myocardial dysfunction developed in both groups. However, recovery of myocardial function-comparing baseline with 120 minutes postresuscitation-was better in pigs treated with EPO than NaCl, as shown for left ventricular ejection fraction (from 45 ± 8% to 36 ± 9% in EPO, not significant; and from 46 ± 8% to 26 ± 8% in NaCl, P < 0.001) and for peak systolic pressure/end-systolic volume (from 2.7 ± 0.8 mmHg/mL to 2.4 ± 0.7 mmHg/mL in EPO, not significant; and from 3.0 ± 1.1 mmHg/mL to 1.8 ± 0.6 mmHg/mL, P < 0.001 in NaCl). The EPO effect was associated with significantly higher myocardial O2 consumption (12 ± 6 mL/min/unit of tissue vs 6 ± 2 mL/min/unit of tissue, P < 0.017) without effects on myocardial lactate consumption. Thus, EPO administered during resuscitation from ventricular fibrillation lessened postresuscitation myocardial stunning-an effect that could be useful clinically to help promote postresuscitation hemodynamic stability.
我们使用开胸猪模型研究了心肺复苏过程中给予促红细胞生成素（EPO）对代谢和功能心肌的影响，该模型通过体外循环复苏心室颤动，并且我们曾在大鼠中报告过，EPO 可逆转与线粒体保护途径激活相关的复苏后心肌功能障碍。在 16 只雄性家猪中诱导心室颤动，并且不进行处理 8 分钟，之后开始并维持体外循环 10 分钟，调整体外循环流量以使冠状灌注压达到 10mmHg。进行除颤，并且在自主循环期间将体外循环流量调整为确保平均主动脉压为 40mmHg 或更高，持续 120 分钟。猪被随机分为 1:1 接受 EPO（1200U/kg）或 0.9%NaCl，然后开始进行体外循环。两组均出现严重的复苏后心肌功能障碍。然而，与复苏后 120 分钟相比，接受 EPO 治疗的猪的心肌功能恢复更好，左心室射血分数（EPO 从 45±8%降至 36±9%，无显著差异；NaCl 从 46±8%降至 26±8%，P<0.001）和峰值收缩压/收缩末期容积（EPO 从 2.7±0.8mmHg/mL 降至 2.4±0.7mmHg/mL，无显著差异；NaCl 从 3.0±1.1mmHg/mL 降至 1.8±0.6mmHg/mL，P<0.001）。EPO 的作用与心肌耗氧量明显增加相关（12±6mL/min/单位组织与 6±2mL/min/单位组织，P<0.017），而不影响心肌乳酸消耗。因此，在心肺复苏过程中给予 EPO 可减轻复苏后心肌顿抑，这种作用在临床上可能有助于促进复苏后血流动力学稳定。
